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1.
C3H/HeN and C57BL/6 mice were exposed to culture filtrate (CF) and mycelial extracts (ME) of Aspergillus fumigatus (Af) intranasally. Animals received 6, 8 or 10 biweekly doses and were sacrificed 2 weeks after the last dose was administered. Specific antibodies against Af were detected in their sera by biotin-avidin-linked immunosorbent assay (BALISA). Antibodies against Af belonging to all isotypes showed an increase in both strains of mice. A progressive increase in IgG and IgA antibody isotypes against both CF and ME antigens was detected in C3H/HeN mice during the entire experimental period, whereas most antibody levels peaked after the 8th dose and remained steady or decreased slightly in the C57BL/6 strain. Lung lavage studies showed a relative decrease in the number of macrophages and an increase in the number of lymphocytes after the 6th and 8th instillation of Af antigens in both strains of mice. Histology of the lung demonstrated a progressive inflammatory reaction in C57BL/6 mice during the experimental period. On the other hand, the C3H/HeN mice showed a negligible inflammatory pulmonary reaction. The antibody responses and inflammatory changes detected in the lungs of mice exposed to Af antigens are comparable to allergic bronchopulmonary aspergillosis (ABPA) in humans and hence this model will be of value in understanding the disease mechanism in ABPA and related diseases.  相似文献   

2.
Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged with PA developed a cellular immune response characterized by elevations in Th1 cytokines/chemokines, increased numbers of lymphocytes and macrophages in lung lavage fluid, and peribronchovascular granulomatous inflammation composed of T- and B-lymphocytes and epithelioid histiocytes. T-lymphocytes in the lung lavage fluid showed a marked CD4+ cell predominance. In contrast, C57BL/6 mice challenged with Staphylococcus epidermidis (SE), another gram-positive commensal of human skin, and BALB/c mice challenged with PA, showed only a modest induction of Th1 cytokines, less pulmonary inflammation, and no granulomatous changes in the lung. Enhancement of Toll-like receptor expression was seen in PA-exposed C57BL/6 mice within 24 h after exposure, suggesting that induction of innate immunity by PA contributes to the robust, polarized Th1 immune response elicited by this bacterium. These findings suggest that PA-induced pulmonary inflammation may be a useful model for testing the contributions of both bacterial and host factors in the development, maintenance, and resolution of granulomatous inflammation in the lung.  相似文献   

3.
Using a nonlethal systemic Aspergillus fumigatus infection, we have recently shown that similarly efficient elimination of fungus from spleens of prototypic Th1 (C57BL/6) and prototypic Th2 (BALB/c) mice is associated with differential immune responses. In light of these data and given the disseminated character of infection, the aim of the present study is to explore whether there are also strain‐dependent differences in antifungal responses in peripheral tissues of infected mice. Although similar efficiency of conidia removal was noted in liver and kidneys of both strains, BALB/c mice seemed more prone to tissue injury. Compared with other nonlymphoid organs, lungs proved immunologically the most responsive in systemic aspergillosis. Lower numbers of neutrophils and macrophages in the lungs of infected BALB/c mice, delayed and lower (compared with C57BL/6 mice) expression of their oxidative activity, along with late IFN‐γ and upregulated IL‐4 production by lung cells might be responsible for slower elimination of A. fumigatus from the lungs of this mouse strain. The data obtained imply that lungs should be viewed as mandatory organ in evaluation of immune‐mediated antifungal potential of drugs in models of systemic/disseminated infection and that strain differences noted in tissue responses should be taken into account in these settings.  相似文献   

4.
Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice, volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6 mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of adaptive processes and different sensitivity of these mice to pathogenic agents.  相似文献   

5.
In the present study, we used a dry maze task to assess the spatial learning ability of C57BL/6N and BALB/cA mice besides the water maze task. In Experiment 1, the performance of C57BL/6N and BALB/cA mice in the water maze task and dry maze task were investigated. In the former task, the mice had to learn the position of a hidden platform submerged below the water surface and they had to learn the position of a baited hole on the circular maze in the latter task. C57BL/6N mice showed significant learning in both maze tasks, whereas BALB/cA mice showed learning in a dry maze but not in water maze as reported before. In Experiment 2, a dry maze task was conducted on a circular open field which contained 16 holes arranged symmetrically and which was put on the same height as the surface of the water maze. In Experiment 2, BALB/cA mice showed significant improvement in latency and path length to reach the food hole. The poor performance of the BALB/cA in the water maze task may reflect a weak motivation, escaping from water, rather than the poor spatial memory in this strain.  相似文献   

6.
In this study, histopathological bronchial-bronchiolar lesions of the late asthmatic responses induced by ovalbumin in BALB/c and C57BL/6 mice were compared. Prominent goblet cell hyperplasia and metaplasia with mucous secretion, and desquamation of epithelial cells with severe infiltration of eosinophils and lymphocytes, were observed in the BALB/c mice; in the C57BL/6 mice, however, these changes were less severe. The reduced histopathological changes in the C57BL/6 mice were associated with a decreased infiltrate of eosinophils, decreased serum immunoglobulin-E (IgE) concentrations and increased serum interferon-gamma concentrations. The results suggest that the reduced bronchial lesions in C57BL/6 mice were due, at least in part, to suppression of the T-helper (Th)2 immune response that underlies the decreased infiltration of lymphocytes and eosinophils into the bronchial mucosa.  相似文献   

7.
The cilium-associated respiratory (CAR) bacillus is a gram-negative, gliding bacterium that causes persistent respiratory tract infections in rodents despite histologic and serologic evidence of a marked immune response. To assess humoral immunity and cytokine responses in CAR bacillus disease, 6-week-old female BALB/c and C57BL/6 mice were inoculated intratracheally with 10(5) CAR bacillus organisms. CAR bacillus-specific serum immunoglobulins (immunoglobulin M [IgM], IgG1, IgG2a, IgG2b, IgG3, and IgA) and local pulmonary cytokines (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], and interleukin-4 [IL-4]) were evaluated by enzyme-linked immunosorbent assay every 7 days for 49 days. BALB/c mice developed CAR bacillus-induced lesions early in the course of disease that became more severe with time. Correlating with increasing disease severity, BALB/c mice had elevations in all antibody isotypes tested, and elevations in pulmonary TNF-alpha, IFN-gamma, and IL-4. C57BL/6 mice developed mild lesions with mild increases in serum IgM, IgG1, IgG2b, and IgG3 levels and minimally detectable IgG2a and IgA. Cytokine perturbations were not detected in C57BL/6 mice. The persistence of infection in BALB/c mice with vigorous serum antibody responses and increased IFN-gamma and IL-4 responses suggests that humoral immunity and T-cell responses are ineffective at preventing CAR bacillus disease. Furthermore, the lackluster antibody responses and undetectable cytokine responses in C57BL/6 mice suggest that humoral immunity and T-cell responses are not critical in resistance to CAR bacillus-induced disease.  相似文献   

8.
9.
BACKGROUND: BALB/c and C57BL/6 mice are two inbred strains, but after voluntary movement, there is no report on how to scientifically reasonably select behavioral experiment methods and indicators and to evaluate the learning and memory abilities of mice.  相似文献   

10.
We characterized liver-infiltrating leucocytes (LIL) from BALB/c and C57BL/6 mice 0-56 days after murine cytomegalovirus (MCMV) infection. Inflammation clears from C57BL/6 mice 4-5 weeks post infection (pi), but persists for several months in BALB/c mice. The LIL obtained were 60-80% Thy 1.2+ by flow cytometry. The percentage of CD8+ cells rose sharply in all mice 7 days pi, with little decrease in BALB/c mice by day 56. CD4-CD8-Thy 1.2+/TCR alpha beta + cells were more prevalent in LIL than lymph node cells (LNC) irrespective of MCMV infection, whilst infection increased the proportion of CD8+ L-selectin- LIL (but not LNC). LIL from both mouse strains demonstrated cytotoxic activity against YAC-1 cells, but only LIL from BALB/c mice proliferated spontaneously ex vivo 21 days pi, as measured by tritiated thymidine incorporation. BALB/c LIL produced IFN gamma and IgG2a 7-21 days pi, whilst IL-10 secretion was similar in both strains. Thus, persistent hepatitis in BALB/c mice is associated with activation and proliferation of intrahepatic leucocytes with some bias towards a Th1 response.  相似文献   

11.
After infection with a low-virulence strain of Mycobacterium avium, C57BL/6 and C57BL/10 mice had clear differences in the control of the infection in their livers and spleens. This difference in susceptibility was not associated with differences in the H-2 complex. It was dependent on the activity of CD4(+) T cells but unrelated to the ability of these cells to secrete gamma interferon or to the development of delayed-type hypersensitivity responses at 3 weeks of infection. It was associated with lower total numbers of CD4(+) cells present in infected spleens and was related to an earlier induction of protective T cells, as measured by adoptive-transfer assays. These data further strengthen the notion of gamma-interferon-independent mechanisms of protection against mycobacteria.  相似文献   

12.
Inoculation of Trypanosoma cruzi, Tulahuén strain, into C57BL/6 and BALB/c mice led to an acute infection characterized by marked parasitaemia, myocardial inflammation and thymocyte depletion. While C57BL/6 mice showed a progressive and lethal disease, BALB/c mice partly recovered. To characterize these murine models more effectively, we studied the parasite burden, serum levels of major infection outcome-related cytokines, the in vitro features of T. cruzi infection in peritoneal macrophages and the immunophenotype of thymic cells. The greater disease severity of T. cruzi-infected C57BL/6 mice was not linked to an increased parasite load, as parasitaemia, myocardial parasite nests and amastigote counts in peritoneal macrophages were not different from those in BALB/c mice. Cortical thymocyte loss was accompanied by the presence of apoptotic bodies and fragmented nuclear DNA, whereas fluorocytometric analysis at 17 days postinfection (p.i.) revealed a more pronounced loss of CD4+ CD8+ cells in C57BL/6 mice. This group displayed higher levels of TNF-alpha on days 14 and 21 p.i., in the presence of lower IL-1beta and IL-10 concentrations by days 14 and 21, and days 7 and 14 p.i., respectively. Day-21 evaluation showed higher concentrations of nitrate and TNF-alpha soluble receptors in C57BL/6 mice with no differences in IFN-gamma levels, with respect to the BALB/c group. Increased morbidity of C57BL/6 T. cruzi-infected mice does not seem to result from an aggravated infection but from an unbalanced relationship between pro- and anti-inflammatory mediators.  相似文献   

13.
Mycobacterium massiliense is an environmental opportunistic pathogen that has been associated with soft tissue infection after minor surgery. We studied the acute immune response of C57BL/6 and BALB/c mice infected intravenously with 106 CFU of an M. massiliense strain isolated from a nosocomial infection in Brazil. The results presented here show that M. massiliense is virulent and pathogenic to both C57BL/6 and BALB/c mice, inducing a granulomatous inflammatory reaction that involves the activation of macrophages, dendritic cells, and natural killer cells induced by gamma interferon and interleukin-17 (IL-17) in C57BL/6 mice and by IL-12 in BALB/c mice.Mycobacteria that do not belong to the complex Mycobacterium tuberculosis are known as nontuberculous mycobacteria (NTM) or atypical mycobacteria. NTM are ubiquitous microorganisms found worldwide in soil and water (3, 23, 38). These environmental mycobacteria are considered emerging and environmental opportunistic pathogens (6, 23).Mycobacterium massiliense is an environmental nonphotochromogenic, rapidly growing Mycobacterium strain that has been associated with soft-tissue infection after minor surgery or intramuscular injection (3, 5, 17, 22, 26, 46) and with pulmonary infection due to diseases, such as cystic fibrosis (29, 41). This species differs only slightly from Mycobacterium abscessus, sharing a 99.6% sequence identity of their 16S rRNA genes; genetic differences can be observed by comparative sequence analysis of the rpoB and hsp65 genes (1, 25, 42). Infections with these agents tend to respond poorly to macrolide-based chemotherapy (3), even though the organisms are susceptible to clarithromycin (15, 44, 47).M. massiliense infection mainly affects immunocompetent individuals and occasionally is associated with disseminated disease (8). An outbreak of M. massiliense occurred in Goiania, Brazil, where 30 individuals were infected after undergoing knee joint and laparoscopic surgery (5). Despite the fact that the infected individuals were from different hospitals, a unique M. massiliense strain was identified and characterized by pulsed-field gel electrophoresis.Disease pathogenesis involves host-pathogen interactions that directly affect parasite clearance. Typically, when environmental bacteria are passively introduced into the host, rapid bacterial clearance occurs due to an efficient innate immune response (30). Nonetheless, accidental infections with M. massiliense have been described as having a chronic evolution and, in some cases, the disease is disseminated irrespective of the host''s immune status. Such findings raise the possibility that this species is more virulent and/or pathogenic than other environmental mycobacteria, such as M. chelonae and M. abscessus.Recently, a murine model of M. abscessus infection was described, and isogenic mice were shown to be good models to address the immune response of the host (34, 39). In the present study, we analyzed the immune response of C57BL/6 and BALB/c mice infected with a clinical isolate of M. massiliense obtained from the recent outbreak in Goiania, Brazil. We show here that M. massiliense is virulent and pathogenic to both C57BL/6 and BALB/c mice, inducing a granulomatous inflammatory reaction that involves the activation of macrophages, dendritic cells (DCs), and natural killer (NK) cells induced mainly by gamma interferon (IFN-γ) and interleukin-17 (IL-17) in C57BL/6 mice and by IL-12 in BALB/c mice.  相似文献   

14.
Brucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock-out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon-γ (IFN-γ), perforin or β2-microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN-γ knock-out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post-infection. These mice had a continual increase in the number of bacterial colony-forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-γ gene were infected they had more splenic CFU at one week post-infection than control mice but the increase was not statistically significant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN-γ knock-out mice between 6 and 10·5 weeks, although they died at 10·5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN-γ gene disrupted mice coincided with symptoms of cachexia and macrophages comprised ≥75% of the splenic leucocytes.  相似文献   

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16.
为了进一步研究实验性变态反应性脑脊髓炎(EAE)动物模型,采用从新鲜牛脊髓中提取的MBP免疫诱导非敏感品系BALB/c小鼠和C57BL/6小鼠,通过对实验动物的症状、中枢神经系统的病理改变及细胞因子水平变化的检测,较成功地建立了C57BL/6、BALB/c小鼠的EAE模型,实验方法稳定可靠。  相似文献   

17.
The current study was designed to investigate the impact of genetic heterogeneity on host immune responses to pulmonary intracellular infection by using two mouse strains of distinct genetic background, C57BL/6 and BALB/c mice, and a model intracellular pathogen, Mycobacterium bovis BCG. Upon infection, compared to C57BL/6 mice, BALB/c mice developed an earlier response of interleukin 12 (IL-12), gamma interferon (IFN-gamma), tumor necrosis factor alpha, and macrophage chemoattractive protein 1, and greater neutrophilic influx to the lung by days 7 and 14. However, the level of these cytokines at days 27, 43, and 71 was much lower in BALB/c mice than in C57BL/6 mice. The magnitude of cellular responses was also much lower in the lung of BALB/c mice around day 27. Histologically, while C57BL/6 mice developed lymphocytic granulomas, BALB/c mice displayed atypical granulomas in the lung. Of importance, the level of type 2 cytokines IL-4 and IL-10 remained low and similar in the lung of both C57BL/6 and BALB/c mice throughout. Furthermore, lymphocytes isolated from systemic and local lymphoid tissues of infected BALB/c mice demonstrated a markedly lower antigen-specific IFN-gamma recall response. While the number of mycobacterial bacilli recovered from both the lung and spleen of BALB/c mice was similar to that in C57BL/6 mice at day 14, it was higher than that in C57BL/6 mice at day 43. However, it was eventually leveled off to that in C57BL/6 counterparts later. These results suggest the following: (i) genetic heterogeneity can lead to differential innate and adaptive cell-mediated immune responses to primary pulmonary mycobacterial infection; (ii) it is the level of adaptive, but not innate, immune response that is critical to host resistance; and (iii) a lower type 1 immune response in BALB/c mice is not accompanied by a heightened type 2 response during pulmonary mycobacterial infection.  相似文献   

18.
The vitamin A metabolite retinoic acid (RA) has been reported to suppress Th1 responses and enhance Th2 responses. Here, we investigated whether differences in vitamin A metabolism could underlie the differences between C57BL/6 and BALB/c mice, which are reportedly seen as Th1 and Th2 responders, respectively. BALB/c mice were shown to have higher intestinal epithelial expression of RALDH1 (where RALDH is retinaldehyde dehydrogenase), and, consequently, higher RALDH activity in MLN‐DCs, leading to an increased ability to induce IgA class switching in B cells. Furthermore, within BALB/c mice, induction of IgA secretion as well as increased accumulation of regulatory T cells (Treg) in the intestinal lamina propria was observed. Additionally, as BALB/c mice are more resistant to dextran sulphate sodium (DSS) induced colitis, mice that lacked vitamin A in their diet had a more severe form of DSS‐induced colitis compared to control mice. Therefore, the level of RA production and consequently the degree of RA‐mediated signaling is crucial for the efficiency of the mucosal immune system.  相似文献   

19.
Compared to C57BL/6 mice, BALB/c mice exhibit greater 'anxiousness' on behavioural tests of anxiety, and can show significantly longer sleep disruptions after exposure to anxiogenic situations. Relative to C57BL/6 mice, BALB/c mice also have reduced benzodiazepine (BZ) receptor densities in the brain and fivefold less BZ receptor density in the amygdala, a region important in anxiety and in the control of arousal. Lorazepam is a BZ receptor full agonist and has been used to treat both anxiety and insomnia. Differences between C57BL/6 and BALB/c mice raise the question of whether BZ agonists would impact sleep and activity differentially in the two strains. We examined the effects of two doses of lorazepam (0.5 and 1.5 mg kg−1) or saline alone (0.2 mL) on sleep and activity in C57BL/6 ( n  =   8) and BALB/c ( n  =   7) mice. Compared to saline, both doses of lorazepam significantly increased non-rapid eye movement (NREM) and reduced activity in both strains. In C57BL/6 mice, rapid eye movement (REM) was increased at both doses. In BALB/c mice, the 0.5 mg kg−1 dose had no significant influence on REM, whereas REM was reduced significantly after the 1.5 mg kg−1 dose. The results demonstrate significant differences between C57BL/6 and BALB/c mice in the effects of lorazepam on REM, whereas the effects on NREM and activity were similar. Strain differences in the number of BZ receptors in the amygdala, but not other brain regions, suggests possible site specificity in the effects of lorazepam on REM. These differences in BZ-binding sites in the amygdala could be a significant factor in differences in the sleep response between C57 and BALB/c mice.  相似文献   

20.
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